Kinetic evaluation and assessment of longitudinal changes in reference region and extracerebral [18F]MK-6240 PET uptake.

[18F]MK-6240 meningeal/extracerebral off-target binding may impact tau quantification. We examined the kinetics and longitudinal changes of extracerebral and reference regions. [18F]MK-6240 PET was performed in 24 cognitively-normal and eight cognitively-impaired subjects, with arterial samples in 13 subjects. Follow-up scans at 6.1 ± 0.5 (n = 25) and 13.3 ± 0.9 (n = 16) months were acquired. Extracerebral and reference region (cerebellar gray matter (CerGM)-based, cerebral white matter (WM), pons) uptake were evaluated using standardized uptake values (SUV90-110), spectral analysis, and distribution volume. Longitudinal changes in SUV90-110 were examined. The impact of reference region on target region outcomes, partial volume correction (PVC) and regional erosion were evaluated. Eroded WM and pons showed lower variability, lower extracerebral contamination, and lower longitudinal changes than CerGM-based regions. CerGM-based regions resulted larger cross-sectional effect sizes for group differentiation. Extracerebral signal was high in 50% of subjects and exhibited irreversible kinetics and nonsignificant longitudinal changes over one-year but was highly variable at subject-level. PVC resulted in higher variability in reference region uptake and longitudinal changes. Our results suggest that eroded CerGM may be preferred for cross-sectional, whilst eroded WM or pons may be preferred for longitudinal [18F]MK-6240 studies. For CerGM, erosion was necessary (preferred over PVC) to address the heterogenous nature of extracerebral signal.

Multimodal Investigation of Neuroinflammation in Aviremic Patients With HIV on Antiretroviral Therapy and HIV Elite Controllers.

BACKGROUND AND OBJECTIVES: The presence of HIV in the CNS has been related to chronic immune activation and cognitive dysfunction. The aim of this work was to investigate (1) the presence of neuroinflammation in aviremic people with HIV (PWH) on therapy and in nontreated aviremic PWH (elite controllers [ECs]) using a translocator protein 18 kDa radioligand; (2) the relationship between neuroinflammation and cognitive function in aviremic PWH; and (3) the relationship between [11C]-PBR28 signal and quantitative MRI (qMRI) measures of brain tissue integrity such as T1 and T2 relaxation times (rts). METHODS: [11C]-PBR28 (standard uptake value ratio, SUVR) images were generated in 36 participants (14 PWH, 6 ECs, and 16 healthy controls) using a statistically defined pseudoreference region. Group comparisons of [11C]-PBR28 SUVR were performed using region of interest-based and voxelwise analyses. The relationship between inflammation, qMRI measures, and cognitive function was studied. RESULTS: In region of interest analyses, ECs exhibited significantly lower [11C]-PBR28 signal in the thalamus, putamen, superior temporal gyrus, prefrontal cortex, and cerebellum compared with the PWH. In voxelwise analyses, differences were observed in the thalamus, precuneus cortex, inferior temporal gyrus, occipital cortex, cerebellum, and white matter (WM). [11C]-PBR28 signal in the WM and superior temporal gyrus was related to processing speed and selective attention in PWH. In a subset of PWH (n = 12), [11C]-PBR28 signal in the thalamus and WM regions was related to a decrease in T2 rt and to an increase in T1 rt suggesting a colocalization of increased glial metabolism, decrease in microstructural integrity, and iron accumulation. DISCUSSION: This study casts a new light onto the role of neuroinflammation and related microstructural alterations of HIV infection in the CNS and shows that ECs suppress neuroinflammation more effectively than PWH on therapy.

Performance Invalidity Base Rates Among Healthy Undergraduate Research Participants.

Few studies have examined base rates of suboptimal effort among healthy, undergraduate students recruited for neuropsychological research. An and colleagues (2012, Conducting research with non-clinical healthy undergraduates: Does effort play a role in neuropsychological test performance? Archives of Clinical Neuropsychology, 27, 849-857) reported high rates of performance invalidity (30.8%-55.6%), calling into question the validity of findings generated from samples of college students. In contrast, subsequent studies have reported much lower base rates ranging from 2.6% to 12%. The present study replicated and extended previous work by examining the performance of 108 healthy undergraduates on the Dot Counting Test, Victoria Symptom Validity Test, Word Memory Test, and a brief battery of neuropsychological measures. During initial testing, 8.3% of the sample scored below cutoffs on at least one Performance Validity Test, while 3.7% were classified as invalid at Time 2 (M interval = 34.4 days). The present findings add to a growing number of studies that suggest performance invalidity base rates in samples of non-clinical, healthy college students are much lower than An and colleagues initial findings. Although suboptimal effort is much less problematic than suggested by An and colleagues, recent reports as high as 12% indicate including measures of effort may be of value when using college students as participants. Methodological issues and recommendations for future research are presented.